Glaucoma is a leading cause of blindness in the US. Traditional methods of glaucoma diagnosis and monitoring lack good sensitivity and specificity. Delays in detecting glaucoma progression can lead to inadequate treatment and irreversible visual loss. Our goal is to improve glaucoma diagnosis by utilizing new imaging modalities that can reveal changes in the retinal layers affected by glaucoma and the associated reduction in retinal blood flow. Glaucoma selectively damages the retinal nerve fibers, which originate from cell bodies in ganglion cell layer (GCL) and travel to the optic nerve via the nerve fiber layer (NFL). We hypothesize that subtle damages in these structures can be detected earlier by optical coherence tomography (OCT) and other advanced imaging modalities than with current standard methods. OCT is based on infrared light reflectometry. It provides micrometer-scale cross-sectional images of retinal structures, which are not possible with other non-invasive techniques. More than 7,000 OCT systems are already being used for the diagnosis of glaucoma and retinal diseases. Phase I of the Advanced Imaging for Glaucoma (AIG) study demonstrated that peripapillary NFL thickness measured with the standard timedomain (TD) OCT technology has higher glaucoma diagnostic accuracy than other quantitative diagnostic technologies such as scanning laser polarimetry (SLP) and scanning laser tomography (SLT). We also demonstrated that more advanced diagnostic software and faster Fourier-domain (FD) OCT systems can achieve even better diagnostic accuracy and reproducibility. In the proposed Phase II of the AIG study, we will continue the most promising aspects of the research to further improve both technology and clinical practice.